Cognitive Reserve Is Protective Of Cognition And Frontal Grey Matter In Amyotrophic Lateral Sclerosis

OBJECTIVE: To evaluate whether cognitive reserve (CR) is associated with cognition and frontal grey matter (GM) in amyotrophic lateral sclerosis (ALS).BACKGROUND: Evidence suggests a clinicopathological spectrum between ALS and frontotemporal degeneration (FTD): approximately 40[percnt] of ALS patients have mild cognitive impairment (MCI) or FTD, and both diseases share TDP-43 pathology. However, the mechanisms underlying cognitive heterogeneity in ALS remain unclear. CR, a measurement of lifetime intellectual experience, is associated with longer survival, less GM atrophy, and better cognition in FTD, but has not been investigated in ALS. We hypothesized CR would also be protective of cognition and frontal GM in ALS.DESIGN/METHODS: We evaluated 98 ALS patients and 183 controls with T1 MRI processed using ANTs to compute GM density; a subset of patients completed Edinburgh Cognitive Assessment Scale (ECAS;N=23) and ALS-functional rating scale (ALS-FRS-R;N=95). We assessed CR using a composite measure of education and occupation, and explored relationships between CR and rating scales using regression. We identified GM atrophy in ALS relative to controls using voxelwise t-tests, and used regression to identify GM density associated with greater CR. All analyses controlled for age, disease duration, and bulbar onset.RESULTS: CR predicted better performance on ECAS (95[percnt]CI: 0.22, 7.11; t=2.24, p=0.04) but not ALS-FRS-R (95[percnt]CI: -0.48, 1.19; t=0.85, p=0.40) in ALS. ALS patients had GM atrophy in bilateral frontal and anterior cingulate cortex (pu003c0.05 fwe-corrected) and CR predicted higher GM density in bilateral orbitofrontal, lateral temporal, and anterior cingulate cortex (pu003c0.01).CONCLUSIONS: CR is protective of cognition and frontal GM in ALS patients, consistent with evidence indicating a protective role of CR in FTD and with models viewing ALS and FTD along a spectrum. Identifying protective factors associated with ALS and FTD is important for prognosis and treatment.STUDY SUPPORT: NIH(AG043503, AG017586, AG010124, AG032953,NS063111), Dana Foundation and Wyncote Foundation. Disclosure: Dr. Placek has nothing to disclose. Dr. Ternes has nothing to disclose. Dr. Olm has nothing to disclose. Dr. Massimo has nothing to disclose. Dr. Woo has nothing to disclose. Dr. Elman has nothing to disclose. Dr. McCluskey has nothing to disclose. Dr. Irwin has nothing to disclose. Dr. Grossman has received personal compensation for activities with GE Whitney Symposium as an invited speaker. Dr. Grossman has received personal compensation in an editorial capacity for Neurology. Dr. McMillan has nothing to disclose.